Asymptotic and numerical analysis of a simple model for blade coating

Motivated by the industrial process of blade coating, the two-dimensional flow of a thin film of Newtonian fluid on a horizontal substrate moving parallel to itself with constant speed under a fixed blade of finite length in which the flows upstream and downstream of the blade are coupled via the flow under the blade is analysed. A combination of asymptotic and numerical methods is used to investigate the number and nature of the steady solutions that exist. Specially, it is found that in the presence of gravity there is always at least one, and (depending on the parameter values) possibly as many as three, steady solutions, and that when multiple solutions occur they are identical under and downstream of the blade, but differ upstream of it. The stability of these solutions is investigated, and their asymptotic behaviour in the limits of large and small flux and weak and strong gravity effects, respectively, determined

Increased entropy of signal transduction in the cancer metastasis phenotype

Studies into the statistical properties of biological networks have led to important biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis. Further exploration of such integrated cancer expression and protein interaction networks will therefore be a fruitful endeavour.Comment: 5 figures, 2 Supplementary Figures and Table

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Innate Immune Responses of Pulmonary Epithelial Cells to Burkholderia pseudomallei Infection

10.1371/journal.pone.0007308PLoS ONE410

ALCAM (CD166) Expression and Serum Levels in Pancreatic Cancer

BACKGROUND: This study was conducted to evaluate the expression of the activated leukocyte cell adhesion molecule (ALCAM) in pancreatic cancer (PAC) and to determine whether or not the ectodomain shedding of ALCAM (s-ALCAM) could serve as a biomarker in the peripheral blood of PAC patients. MATERIAL AND METHODS: Tissue specimens and blood sera of patients with PAC (n = 264 and n = 116, respectively) and the sera of 115 patients with chronic pancreatitis (CP) were analyzed via ALCAM immunohistochemistry and s-ALCAM ELISA tests. Results were correlated with clinical, histopathological, and patient survival data (Chi-square test, Kaplan-Meier analysis, log-rank test, respectively). RESULTS: ALCAM was expressed in the majority of PAC lesions. Immunohistochemistry and serum ELISA tests revealed no association between ALCAM expression in primary tumors or s-ALCAM and clinical or histopathological data. Neither ALCAM nor s-ALCAM showed a significant impact regarding overall survival (p = 0.261 and p = 0.660, respectively). S-ALCAM serum levels were significantly elevated compared to the sera of CP patients (p<0.001). The sensitivity of s-ALCAM in detecting PAC was 58.6% at a specificity of 73.9% (AUC = 0.69). CONCLUSIONS: ALCAM is expressed in the majority of PAC lesions, but statistical analysis revealed no association with clinical or pathological data. Although significantly elevated in patients with PAC, the sensitivity and specificity of the s-ALCAM serum quantification test was low. Therefore, its potential as a novel diagnostic marker for PAC remains elusive and further investigations are required

Breast Cancer Epigenetics: From DNA Methylation to microRNAs

Both appropriate DNA methylation and histone modifications play a crucial role in the maintenance of normal cell function and cellular identity. In cancerous cells these “epigenetic belts” become massively perturbed, leading to significant changes in expression profiles which confer advantage to the development of a malignant phenotype. DNA (cytosine-5)-methyltransferase 1 (Dnmt1), Dnmt3a and Dnmt3b are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells. Intriguingly, DNMTs were found to be overexpressed in cancerous cells, which is believed to partly explain the hypermethylation phenomenon commonly observed in tumors. However, several lines of evidence indicate that further layers of gene regulation are critical coordinators of DNMT expression, catalytic activity and target specificity. Splice variants of DNMT transcripts have been detected which seem to modulate methyltransferase activity. Also, the DNMT mRNA 3′UTR as well as the coding sequence harbors multiple binding sites for trans-acting factors guiding post-transcriptional regulation and transcript stabilization. Moreover, microRNAs targeting DNMT transcripts have recently been discovered in normal cells, yet expression of these microRNAs was found to be diminished in breast cancer tissues. In this review we summarize the current knowledge on mechanisms which potentially lead to the establishment of a DNA hypermethylome in cancer cells

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Geographical variation in shell shape of the pod razor shell Ensis siliqua (Bivalvia: Pharidae)

The present study assessed the existence of variation in the shell shape of the pod razor shell (Ensis siliqua) throughout its distributional range in the north- eastern Atlantic. Shells of E. siliqua caught at seven collecting sites (three in Portugal, three in Spain and one in Ireland) were studied by geometric morphometric methods, using both landmark- and contour-based methods. Both approaches (landmarks inside the valves and shell outline) discriminated the shells from Aveiro (centre of Portugal) and Strangford Lough (Ireland) from those caught in the nearby localities (remaining Portuguese and Spanish sites,maximum distance of 550 km by sea). Landmark analysis revealed that shells from Aveiro were more similar to shells from Ireland (*1,500 km far away). Contour anal- ysis revealed that shells from Aveiro had a shape with a comparatively larger height-to-width ratio, whereas shells from Ireland showed a slightly more curved outline than in the remaining sites. Landmark- and contour-based methods provided coherent complementary information, confirming the usefulness of geometric morphometric analyses for discerning differences in shell shape among populations of E. siliqua. A brief review of previous applications of geometric morphometric methods to modern bivalve spe- cies is also provided.The authors would like to thank Dr. Dai Roberts and Adele Cromie for providing samples of pod razor shells from Ireland. This study was funded by Community Initiative Programmes (INTERREG-IIIB, Atlantic Area) Sustainable HARvesting of Ensis (090–SHARE) and Towards Integrated Management of Ensis Stocks (206–TIMES) from the European Community. Marta M. Rufino and Paulo Vasconcelos benefited from postdoctoral grants (SFRH/BPD/14935/2004 and SFRH/BPD/26348/2006, respectively) awarded by the Fundação para a Ciência e Tecnologia (FCT—Portugal). Finally, the authors acknowledge three anonymous referees for valuable comments and suggestions that greatly improved the revised manuscript.publishe